Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: Final results from a randomised phase ii study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan (FNCLCC ACCORD 13/0503 study)

Abstract Background The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC. Patients and Methods Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m 2 on day 1 and oral capecitabine 1000mg/m 2 bid on days 1–14) every 3weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m 2 on day 1 plus 2400mg/m 2 as a 46-h infusion, leucovorin 400mg/m 2 on day 1, and irinotecan 180mg/m 2 on day 1) every 2weeks. Patients aged ⩾65years received a lower dose of capecitabine (800mg/m 2 twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate. Results A total of 145 patients were enrolled (bevacizumab–XELIRI, n =72; bevacizumab–FOLFIRI, n =73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71–90%) in the bevacizumab–XELIRI arm and 85% (95% CI 75–92%) in the bevacizumab–FOLFIRI arm. In both the bevacizumab–XELIRI and bevacizumab–FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab–XELIRI 18%; bevacizumab–FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively). Conclusions This randomised non-comparative study demonstrates that bevacizumab–XELIRI and bevacizumab–FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.